Month: April 2013

Like many non-scientists I used to think that sonic hedgehog was a video game. Now I know better thanks to a fascinating study by researchers at Stanford and UC San Francisco.

The researchers were trying to understand how developing cells of the embryo communicate with each other. So they put a fluorescent chemical tag onto a molecule they know is involved in the process, a molecule called a sonic hedgehog protein.

The glow-in-the-dark tag enabled them to see exactly what was going on in the cells in the developing chick, in real time. What they saw was fascinating. They saw the cells sending out long extensions, like skinny fingers reaching out in the dark, to make a connection with other cells.

The discovery was quite unexpected and raises lots of fascinating questions. And that’s the beauty of science. You make one discovery, and it raises questions that could ultimately, hopefully, lead you to a deeper understanding of how our bodies work. The lessons learned from basic science like this is what drives the more disease-focused work. If we don’t know how cells communicate and how our bodies form, we can’t possibly fix what happens when the process goes awry.

The stem cell news is a-buzz today with the story of a young girl who received a synthetic windpipe seeded with her own stem cells. She was born without a functioning windpipe and has lived her 2 1/2 years in intensive care.

She’s not the first to receive such a transplant, but she is the youngest (and based on photos accompanying news stories like this one from ABC news, she’s perhaps the cutest). The first fully synthetic windpipe coated in stem cells was transplanted in 2011, as we wrote about here and since then there have been several more such procedures.

This marrying of synthetic tissues and stem cells is part of a growing field of tissue engineering. The New York Times had a fascinating series of stories last year about the field’s progress, including this one about our grantee Tracy Grikscheit who is working to develop an engineered intestine to help kids born with a short or malfunctioning intestine.

CIRM funds several awards to people attempting to engineer new tissues and organs to replace those that aren’t functioning properly. To help those grantees succeed with their science and with the complex regulations surrounding such therapies, we held a tissue engineering workshop to bring the scientists together. This short video from that workshop gives a snapshot of the types of organs and tissues the scientists are working to fix, and the hurdles they face:

This video illustrates what we wrote in our piece on the first synthetic windpipe back in 2011:

One take-away from this announcement is that a lot of incremental steps are required for every groundbreaking advance. We spend a lot of time in this blog writing about those papers that move research incrementally forward. Last week’s piece on bioengineered intestines is one example of that. This recent transplant is a reminder of where all those small steps are taking us.

Behind every pig-tailed 2 1/2 year-old girl receiving a novel therapy are many years of tiny, incremental steps working toward the perfect synthetic material or the best way of delivering the cells. Those steps sometimes seem slow, but the end result can be amazing.

A.A.

Read more stem cell research news from the California Institute for Regenerative Medicine by visiting our blog at cirmresearch.blogspot.com.

In a world where championship sports teams are idolized and superstar athletes are feted by the media, it was gratifying to see science, students and teachers get their moment in the sun at the White House last week.

These kids are the same ones who are one day going to develop the next generation of household technologies, fuel efficient vehicles and, yes, medical breakthroughs that will change the way we live in the future. CIRM has been investing in high school, college and post-graduate students from the very beginning because we know that the next generation of stem cell therapies are going to come from our next generation of scientists, and so those scientists had better be well trained.

“What we should be talking about is how to keep kids interested and get out of their way as they learn.” … “Acts of curiosity are what make up acts of science,” he said. “Adult scientists are just kids who never grew up.”

It always bothers me when I hear people talking about trying to make science fun for kids. Trying? Who needs to try? Science experiments with kids are a blast. It’s nice to see that attitude on the national stage.

A.A.

Read more stem cell research news from the California Institute for Regenerative Medicine by visiting our blog at cirmresearch.blogspot.com.

The local high school sent its full cheerleading squad to cheer on the Huntington’s disease advocates at the beginning of the walk and, here, to congratulate them as they finished the circuit.

Patients with Huntington’s Disease, their families and friends, and families and friends of patients who had already lost the battle with the deadly disease came together in Irvine Saturday for a walk to raise funds for research and a day of camaraderie pegged to the slogan on their T shirts: Team Hope.

CIRM grantee Leslie Thompson of UC Irvine gave a high note in discussing some of the progress in her lab on understanding the disease. She was part of the consortium of research teams that published a paper earlier this year on using reprogrammed, or iPS, cells made from the skin of Huntington’s patients as a model to successfully mimic the disease in the lab. She is now using those cells to develop screening assays that could be used to test potential therapies. Here’s Thompson giving a short description of this project:

Thompson noted that this year marks the 20th anniversary of finding the mutant Huntington gene. Much of the consortium that made that discovery is still working together and took part in the research that created the iPS cell lines. Thompson herself was a post doctoral fellow on that team two decades ago.

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

Stem cells isolated from blood of breast cancer patients. While most researchers accept the concept of cancer stem cells in blood cancers, some still question their role in solid tumors. In this story, a German team has isolated cells circulating in the blood of breast cancer patients that appear to be responsible for the spread of the tumor. It has been known that the presence of circulating cancer cells in the blood stream resulted in a poor prognosis, but not uniformly. Some patients with these cells do well. The German team found that the poor prognosis directly correlated with those patients who had circulating cells that were identifiable different. The team called these cancer stem cells.

Stem cells restore brain function in mice. A team from Wisconsin turned human embryonic stem cells into brain cells, transplanted them into mice that had brain injuries and found that the mice did better on certain tests of cognitive ability. Here’s more about that work.

White house hosts science fair event. Having long stood on a soapbox for involving young people in science as early as possible, I have to applaud this now-annual event at the White House. Here The New York Timesdescribes one particularly bright 11 year old who has her robot write a doodle for President Obama. The White House also produced a video about the day.

President Barack Obama talks with Evan Jackson, 10, Alec Jackson, 8, and Caleb Robinson, 8, from McDonough, Ga., while looking at exhibits at the White House Science Fair in the State Dining Room, April 22, 2013. The sports-loving grade-schoolers created a new product concept to keep athletes cool and helps players maintain safe body temperatures on the field. (Official White House Photo by Chuck Kennedy)

New science learning center for the public in Marin. The CIRM-funded Buck Institute has opened a new learning center dedicated to help train the next generation of scientists and help inform the public about the stem cell work and other aging research done at the institute. This story shows the public enjoying the opportunity at the center’s opening last Saturday.

Cartoon learning tool for kids. Children from 9 to 92 will enjoy and learn from this animation of a stem cell as a super hero.

Sometimes poetry says it best. This poem in Smithsonian magazine provides a short enjoyable meditation on stem cells.

D.G.

Read more stem cell research news from the California Institute for Regenerative Medicine by visiting our blog at cirmresearch.blogspot.com.

When the University of California, Irvine put the construction of its stem cell building out to bid the recession had hit. The bids were low enough they had funds to add an extra floor. This added a bonus for the taxpayers of California who had funded $27 million toward the building through CIRM. The stem cell institute there did not have the funds or the need to build out that added floor at the time the building opened. But the program grew so quickly and their fundraising has gone well so the build-out has begun, providing space for additional stem cell labs working toward new disease therapies.

To commemorate the event, the stem cell center organized an art reception in the shell space that sits on the fourth floor of the Sue and Bill Gross Hall, named for the lead donor for the building. They lined up 24 stem cell images around the periphery of the space that will soon be three new stem cell labs. Each lab in the three floors below had contributed entries.

The most enjoyable part of the night was unexpected. Yes most the images were beautiful, but the groups had spent time writing captions that varied from describing the passion they found in their work to pure whimsy. My favorite turned on a bit of family narrative for the leader of the research team. Brian Cummings’ team works with neural cells derived from an embryonic stem cell line that was created in Sheffield England and go by the name Shef-3. Brian told me his dad grew up in Sheffield, so their image is titled Roadmap to Sheffield.

A key thing about the cells Brian is using is they are not grown on the layer of animal cells that support most traditional embryonic stem cell lines. And some have been created under what is known as Good Manufacturing Practices. These two features mean that if his cell do appear to repair traumatic brain injury in the lab, he could more readily get permission from the Food and Drug Administration to begin clinical trials in people.

All the images can be purchased by contacting Janice Briggs at jbriggs@uci.edu

Brian Cummings with “NeuroNebulous” on the left and “Roadmap to Sheffield” on the right

From the Jonathan Lakey’s lab “Ruby Isle”, showing an islet cell inside a protective encapsulation. (Visually simple, but I had to included this for my friends with diabetes. This type of encapsulation to protect new insulin producing cells from immune system attack is likely to be key to stem cell therapies for the disease.)

From Mathew Burton-Jones lab “Christmas in the Brain,” with the caption: A blizzard of star-shaped astrocytes (green) dash through the brain to surround jolly and plump beta-amyloid plaques (red) in a mouse model of Alzheimer’s

Okay, maybe it’s no high-stakes game show but a new Smithsonian magazine/Pew Research Center survey that quizzes Americans on their science literacy and their thoughts about education in the U.S. awards us with some insights about our perceptions of the nation’s standing in science and technology.

I won’t divulge any answers, but overall the participants did a passable job on the quiz portion of the survey, answering 9 out of 13 questions correctly about half the time (I’m happy to report that I scored a perfect 13). Men did slightly better than women though women scored equal or better on health related questions. On average, the 65+ age group had the lowest scores while the youngest group (18-29) scored as well as the 30-49 and 50-64 age groups.

With all the dismay over the sad decline of science education in the U.S., I was a bit surprised that it was our senior population that had the worst scores and not those under 30. Are the younger folk actually doing better than we think they are? The other portion of the survey results says “yes”. As Smithsonian writer Terence Monmaney reports:

Asked how 15-year-olds in the United States compare with those in other developed nations on a standardized science test … respondents tended to rank American youths at the bottom of the pack. In fact, they place in the middle, scoring 17th out of the 34 developed nations in 2009, the most recent year for which results are available.

Hurray! We’re not as bad as we imagined! That’s great, right? Well, we may not be in the cellar but 17th out of 34 doesn’t breed a lot of confidence in our science and technology future. The silver lining here is that the overly dim view of our kids’ performance shows that Americans are very aware that science education should be improved. And when asked, “From kindergarten through 12th grade, what one subject should schools emphasize more than they do now”, 45% of those surveyed picked a STEM (science, technology, engineering and math) subject. Pew research director Scott Keeter says this response:

reflects a perception that the U.S. is at risk in those areas, that American superiority might be slipping away and needs to be addressed.

This need for high quality science education is certainly not lost on CIRM. Training the next generation of California stem cell scientists is an important focus of the agency through our Creativity Awards and Bridges to Stem Cell Research programs. By supporting high school, undergraduate, and graduate students in their pursuit of stem cell science, we hope they’ll carry on our grantees’ world-class research to develop stem cell-based therapies that are safe, effective and routine.

T.D.

Read more stem cell research news from the California Institute for Regenerative Medicine by visiting our blog at cirmresearch.blogspot.com.

This image shows proteins on the HIV virus binding receptors on the T cell (source: National Institute of Allergy and Infectious Diseases, National Institute of Health)

Doctors in Minnesota have performed a blood-forming stem cell transplant on a 12 year-old boy with both leukemia and HIV infection that could treat both the cancer and the infection (read more about the news here). The first person to receive such a transplant, Timothy Ray Brown (also known as “the Berlin patient”), has been free of HIV since his transplant in 2008. Brown’s transplant, and those of a handful of people since then, have all been from adult donors. The child in Minnesota received cord blood.

It’s big news, but this transplant and Brown’s before it aren’t the therapy that could become a widespread cure—there aren’t enough of the appropriate donors to treat everyone with the disease.

Instead, they prove the concept that HIV can be eradicated. Two groups in California, both funded by CIRM, are building on these transplants to generate therapies that could be used more broadly.

Here’s how the first two transplants worked. There’s a protein on the outside of T cells (the cells the HIV virus infects) that goes by the cumbersome name of CCR5. The HIV virus latches onto the protein as the first step to infecting the cell. Without CCR5, the virus can’t get in.

As luck would have it, a small number of people—mostly of northern European descent—have a mutation that results in a lack of functional CCR5. These people are naturally immune to HIV infection.

OK, so what does this have to do with stem cell transplants? Stem cells in the bone marrow and in cord blood contain blood-forming stem cells that create all the blood and immune cells of the body. When people with leukemia get a bone marrow transplant, they are also receiving these blood-forming stem cells from another person that rebuilds their blood and immune system. In the case of cancer, their new blood system is now cancer free.

But if that transplant comes from someone who has the CCR5 mutation, then the person’s new immune system will also be resistant to HIV. That’s how Timothy Ray Brown was cleared of his infection. Brown had leukemia and needed a bone marrow transplant, and he was also HIV positive. His doctors in Berlin found a donor who had the CCR5 mutation, and used bone marrow from that donor to cure Brown of both his leukemia and his HIV.

The boy who received the transplant in Minnesota has a similar story. In his case, his doctors found a cord blood donor who matched this patient, and that donor had the CCR5 mutation. That transplant is expected to both treat the boy’s leukemia and clear him of his HIV infection.

The problem is that the CCR5 mutation is rare. There’s unlikely to be enough people (or stored cord blood) with the mutation to be able to treat all HIV positive people.

Still, these cases do show that stem cells containing the CCR5 mutation have the possibility of treating the disease. And if the problem is a shortage of the appropriate stem cells then the answer is obvious: learn how the make stem cells with the mutation in the lab. Then there will be enough for everyone.

That’s the idea behind two disease teams we funded back in 2009. Both teams intend to take blood-forming stem cells out of the bone marrow of people infected with HIV. Then, they are going to alter those cells in the lab so that they carry the CCR5 mutation.

With that step, they create a source of stem cells that are matched to the patient (because they are the patient’s own cells) and that will be resistant to HIV. The doctors will then put those cells back into the patient where they will create a new blood and immune system that resists the infection. And voila! A source of therapeutic cells that doesn’t rely on the small number of people with the naturally occurring mutation.

The difference between our two teams lies in how they are creating the mutation. The end goal is the same, it’s just not clear which approach to creating the mutation will be most effective.

John Zaia, who leads the HIV/AIDS disease team at City of Hope, recently recorded this short description of his project:

Despite the groundbreaking nature of the science, Brown’s advice to the young boy before his procedure was routine. The Washington Blade reported him telling the boy:

“When I had my procedure done, I got caught up in the trap of lying around in my bed in the hospital watching television and not exercising. Make sure as soon as you are able, get out of bed and do some exercise, go do what you love, go play some basketball.”

Here’s more about CIRM’s funding commitments to HIV/AIDS and descriptions of the disease team projects: HIV/AIDS Fact Sheet.

A.A.

Read more stem cell research news from the California Institute for Regenerative Medicine by visiting our blog at cirmresearch.blogspot.com.

Today Harvard’s stem cell scientists announced finding a hormone that could lead to a therapy for type 2 diabetes (we blogged about that here). That’s big news for the 26 million people in the U.S. with the disease.

The question I’ve heard is how this relates to the stem cell agency’s investment in a type 1 diabetes therapy being developed by ViaCyte in La Jolla, CA. So far we’ve committed almost $40 million to ViaCyte’s technology, which they hope to start testing in patients in the next year or two. Here’s a list of those awards.

In type 1 diabetes (often called juvenile diabetes), the body’s immune system attacks and eventually destroys the cells of the pancreas that produce insulin. Without insulin, cells in people with the disease can’t take up sugar from the bloodstream and use it for fuel. They rely on injected insulin to survive. In this video, Sarah Young and Chris Stiehl explain what it means to live with the disease.

ViaCyte has developed a way of maturing embryonic stem cells into pancreatic cells that produce insulin. They then put those cells into a device that will protect them from the body’s immune system. They hope to implant that device under the skin, where it will act like a small pancreas, producing insulin on demand. So far, it works as expected in animals.

ViaCyte shared this image with us, which shows a side view of their cells within the flattened pouch.

By contrast, people with type 2 diabetes still make insulin, but they don’t make enough for all the body’s cells to be able to take up sugar from the blood. Early in the disease, they can take drugs that help the body’s cells use the insulin that’s available, but over time most end up needing to inject additional insulin. Harvard’s discovery, if it proves to be as effective as it seems, would expand the number of pancreatic cells that produce insulin, helping those people produce enough insulin without needing injections several times per day.

The two approaches come at the disease from two different sides: one bumping up the number of existing pancreatic cells, the other implanting new pancreatic cells to replace those that are lost. Given that the American Diabetes Association estimates that the total yearly cost of diabetes in the U.S. is $245 billion, we need as many good approaches as possible to help all people with the disease.

This morning at 12pm Harvard time his prediction was proved right — researchers at the institute had published a paper revealing a hormone that prods stem cells in the pancreas to divide and generate new insulin-producing cells. The work could be big news for people with type 2 (so-called adult onset) diabetes, in which cells of the pancreas can’t produce enough insulin for all the body’s cells. As the disease progresses these people end up injecting insulin to meet their body’s demand for the hormone. 26 million people in the U.S. have the disease, which can lead to blindness, kidney damage, nerve damage and issues with circulation if it’s not controlled properly.

The work was published April 25 in the journal Cell, which kept the paper under tight wraps until the embargo lifted this morning. Harvard had been hinting about the publication on their Facebook page April 19, but because of Cell‘s embargo policies couldn’t post their announcement until after the journal unveiled the paper. Harvard’s Facebook page carried a link to their announcement minutes later.

In their announcement, Harvard’s Doug Melton, who led the work, said:

“If this could be used in people it could eventually mean that instead of taking insulin injections three times a day, you might take an injection of this hormone once a week or once a month, or in the best case maybe even once a year.”

Of course, he also says that so far they’ve only tested the hormone in mice, and youngish ones at that, as Matthias Hebrok, director of the University of California, San Francisco, Diabetes Center points out in a news story about the work in Nature. They hope to start testing the hormone in clinical trials in three to five years. They say it’ll take two years just to produce enough of the hormone, which is called betatropin, to be used in the trials.

A.A.

Read more stem cell research news from the California Institute for Regenerative Medicine by visiting our blog at cirmresearch.blogspot.com.